1. Field of the Invention
The present invention relates to a process for manufacturing N-acyl derivatives of glycines .alpha.-substituted by non-hydroxylated radicals of aromatic nature and the novel products resulting therefrom.
2. Description of the Prior Art
Certain glycines (or .alpha.-aminoacetic acids) substituted at the .alpha. position by non-hydroxylated radicals of aromatic nature, such as phenylglycine or 2-amino 2-phenyl acetic acid, thienylglycine or 2-amino 2-thienyl acetic acid, etc., are used among others as intermediates for the preparation of semi-synthetic penicillins. For this purpose, whether for the separation of the enantiomorphs or for reaction with penicillins, the --NH.sub.2 group has to be protected by means of a group which is subsequently easily hydrolysable, for example an acyl group: the N-acyl derivatives of glycines .alpha.-substituted by radicals with an aromatic nature therefore constitute valuable intermediate products in the preparation of semi-synthetic penicillins. They are customarily obtained by acylation of the corresponding glycines, themselves prepared by the conventional methods of amino acid synthesis.
Among these methods, that of STRECKER and its modification, the method of BUCHERER, have been used for a long time. They consist essentially of reacting an aldehyde, in the first case, with an alkali cyanide and ammonia to obtain an .alpha.-aminonitrile, and in the second case, with an alkali cyanide and ammonium carbonate to obtain a hydantoin, this nitrile or this hydantoin then being hydrolysed in an acid medium (ULLMANNS ENCYKLOPADIE DER TECHNISCHEN CHEMIE -- vol. 3 p. 507). They have the drawback of being rather long and complicated and especially of using as a starting material an aromatic aldehyde, which is an expensive substance.
Recently it has been proposed to prepare N-acyl derivatives of glycines .alpha.-substituted by radicals of an aromatic nature by condensing in an acetic medium, in the presence of sulfuric acid, aromatic compounds, substituted or not, with adduct products of glyoxylic acid and aromatic amides (D. BEN ISHAI, I. SATATI and Z. BERLER, J.C.S. Chem. Comm. No. 9 -- July 5, 1975 -- p. 349), the latter being themselves obtained by the action in an organic solvent medium of glyoxylic acid in the form of the hydrate on aromatic amides (U. ZOLLER and D. BEN ISHAI -- Tetrahedron -- vol. 31 p. 863-866 (1975)). This process enables N-acyl arylglycines to be obtained with satisfactory yields but has a certain number of drawbacks:
the aromatic amides are not manufactured industrially, the acyl residue obtained in utilising them and which disappears in the course of the subsequent utilisation of the N-acyl derivative is unnecessarily heavy and expensive.
the glyoxylic acid in the form of hydrate is no longer an industrial product, it is deliquescent and it is also expensive.
However, it is not possible to use this process with aliphatic amides of low molecular weight and aqueous solutions of glyoxylic acid since the adduct product, glyoxylic acid-aliphatic amide, is much more difficult to prepare and to isolate than the adduct product, glyoxylic acid-aromatic amide.